Deficiency of the bone mineralization inhibitor NPP1 protects mice against obesity and diabetes

Carmen Huesa; Dongxing Zhu; James D. Glover; Mathieu Ferron; Gerard Karsenty; Elspeth M. Milne; José Luis Millan; S. Faisal Ahmed; Colin Farquharson; Nicholas M. Morton; Vicky E. MacRae

doi:10.1242/dmm.017905

Deficiency of the bone mineralization inhibitor NPP1 protects mice against obesity and diabetes

Carmen Huesa
, Dongxing Zhu
, James D. Glover
, Mathieu Ferron
, Gerard Karsenty
, Elspeth M. Milne
, José Luis Millan
, S. Faisal Ahmed
, Colin Farquharson
, Nicholas M. Morton
, Vicky E. MacRae

Research output: Contribution to journal › Article › peer-review

20 Citations (Scopus)

Abstract

The emergence of bone as an endocrine regulator has prompted a re-evaluation of the role of bone mineralization factors in the development of metabolic disease. Ectonucleotide pyrophosphatase/phosphodiesterase-1 (NPP1) controls bone mineralization through the generation of pyrophosphate, and levels of NPP1 are elevated both in dermal fibroblast cultures and muscle of individuals with insulin resistance. We investigated the metabolic phenotype associated with impaired bone metabolism in mice lacking the gene that encodes NPP1 (Enpp1(-/-) mice). Enpp1(-/-) mice exhibited mildly improved glucose homeostasis on a normal diet but showed a pronounced resistance to obesity and insulin resistance in response to chronic high-fat feeding. Enpp1(-/-) mice had increased levels of the insulin-sensitizing bone-derived hormone osteocalcin but unchanged insulin signalling within osteoblasts. A fuller understanding of the pathways of NPP1 could inform the development of novel therapeutic strategies for treating insulin resistance.

Original language	English
Pages (from-to)	1341-50
Number of pages	10
Journal	Disease Models & Mechanisms
Volume	7
Issue number	12
DOIs	https://doi.org/10.1242/dmm.017905
Publication status	Published - 5 Dec 2014
Externally published	Yes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Animals
Bone Remodeling
Bone and Bones
Diabetes Mellitus
Disease Models, Animal
Fibroblasts
Gene Deletion
Glucose
Homeostasis
Hydrolysis
Insulin
Insulin Resistance
Male
Mice
Mice, Knockout
Obesity
Osteoblasts
Osteocalcin
Phenotype
Phosphoric Diester Hydrolases
Pyrophosphatases
Signal Transduction
Journal Article
Research Support, Non-U.S. Gov't

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10.1242/dmm.017905Licence: CC BY

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title = "Deficiency of the bone mineralization inhibitor NPP1 protects mice against obesity and diabetes",

abstract = "The emergence of bone as an endocrine regulator has prompted a re-evaluation of the role of bone mineralization factors in the development of metabolic disease. Ectonucleotide pyrophosphatase/phosphodiesterase-1 (NPP1) controls bone mineralization through the generation of pyrophosphate, and levels of NPP1 are elevated both in dermal fibroblast cultures and muscle of individuals with insulin resistance. We investigated the metabolic phenotype associated with impaired bone metabolism in mice lacking the gene that encodes NPP1 (Enpp1(-/-) mice). Enpp1(-/-) mice exhibited mildly improved glucose homeostasis on a normal diet but showed a pronounced resistance to obesity and insulin resistance in response to chronic high-fat feeding. Enpp1(-/-) mice had increased levels of the insulin-sensitizing bone-derived hormone osteocalcin but unchanged insulin signalling within osteoblasts. A fuller understanding of the pathways of NPP1 could inform the development of novel therapeutic strategies for treating insulin resistance.",

keywords = "Animals, Bone Remodeling, Bone and Bones, Diabetes Mellitus, Disease Models, Animal, Fibroblasts, Gene Deletion, Glucose, Homeostasis, Hydrolysis, Insulin, Insulin Resistance, Male, Mice, Mice, Knockout, Obesity, Osteoblasts, Osteocalcin, Phenotype, Phosphoric Diester Hydrolases, Pyrophosphatases, Signal Transduction, Journal Article, Research Support, Non-U.S. Gov't",

author = "Carmen Huesa and Dongxing Zhu and Glover, \{James D.\} and Mathieu Ferron and Gerard Karsenty and Milne, \{Elspeth M.\} and Millan, \{Jos{\'e} Luis\} and Ahmed, \{S. Faisal\} and Colin Farquharson and Morton, \{Nicholas M.\} and MacRae, \{Vicky E.\}",

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month = dec,

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doi = "10.1242/dmm.017905",

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volume = "7",

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journal = "Disease Models \& Mechanisms",

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AU - Huesa, Carmen

AU - Zhu, Dongxing

AU - Glover, James D.

AU - Ferron, Mathieu

AU - Karsenty, Gerard

AU - Milne, Elspeth M.

AU - Millan, José Luis

AU - Ahmed, S. Faisal

AU - Farquharson, Colin

AU - Morton, Nicholas M.

AU - MacRae, Vicky E.

PY - 2014/12/5

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KW - Animals

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KW - Hydrolysis

KW - Insulin

KW - Insulin Resistance

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KW - Mice

KW - Mice, Knockout

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KW - Signal Transduction

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ER -

Deficiency of the bone mineralization inhibitor NPP1 protects mice against obesity and diabetes

Abstract

UN SDGs

Keywords

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